The liver is a sex-steroid responsive tissue in that the synthesis of specific proteins and the level of certain enzymes are hormone-dependent. In the male, a number of steroid metabolizing enzyme activities are induced by testosterone and suppressed by estrogen. Excess estrogen in the male, therefore, could compromise the ability of the male to metabolize this excess estrogen, a situation which might ultimately result in a loss of sexual integrity. We have characterized the male specific estrogen binding protein (MEB) in liver cytosol; a potential role of this protein is that of a unique mechanism for binding estrogen and thus protecting the hepatocyte against the effects of excess estrogen. In this application we propose to purify MEB, raise antibodies to it and develop a radioimmunoassay (RIA) for this protein. The development of the RIA will provide a probe to determine the in vivo role and fate of this protein. Specifically, we will determine if MEB is a secreted protein, and if so, whether it is cleared from the body and by which route (urine, bile). The in vivo ligands for MEB will be identified by administration of radioactive precursors and subsequent rapid isolation by immunoprecipitation. Further, the RIA will be used to evaluate the levels of NEB as a function of hormonal status and age, and to determine the species specificity of this protein. These studies should define the role of this unique estrogen binding protein in the maintenance of the normal hormonal environment of the male.